EVOCLIN (clindamycin phosphate) Foam, 1%, a topical antibiotic in a foam vehicle, contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram in a vehicle consisting of cetyl alcohol, dehydrated alcohol (ethanol 58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol, pressurized with a hydrocarbon (propane/butane) propellant.

Chemically, clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7 (S)-chloro-substitution of the 7 (R)-hydroxyl group of the parent antibiotic, lincomycin, and has the structural formula represented below:

The chemical name for clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1- methyl- trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L- threo-.-D- galactooctopyranoside 2-(dihydrogen phosphate).

Last updated on RxList: 1/16/2009

EVOCLIN is indicated for topical application in the treatment of acne vulgaris. In view of the potential for diarrhea, bloody diarrhea and pseudomembranous colitis, the physician should consider whether other agents are more appropriate. (See CONTRAINDICATIONS, WARNINGS, and ADVERSE REACTIONS.)

Apply EVOCLIN once daily to affected areas after the skin is washed with mild soap and allowed to fully dry. Use enough to cover the entire affected area.

To Use EVOCLIN:

1. Do not dispense EVOCLIN directly onto your hands or face, because the foam will begin to melt on contact with warm skin.
2. Remove the clear cap. Align the black mark with the nozzle of the actuator.
3. Hold the can at an upright angle and then press firmly to dispense. Dispense an amount directly into the cap or onto a cool surface. Dispense an amount of EVOCLIN that will cover the affected area(s). If the can seems warm or the foam seems runny, run the can under cold water.
4. Pick up small amounts of EVOCLIN with your fingertips and gently massage into the affected areas until the foam disappears.

Throw away any of the unused medicine that you dispensed out of the can. Avoid contact of EVOCLIN with eyes. If contact occurs, rinse eyes thoroughly with water.

EVOCLIN containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is available in the following sizes: 100 gram can - NDC 63032-061-00 and 50 gram can - NDC 63032-061-50

Storage and Handling

Store at controlled room temperature 20°- 25°C (68°- 77°F).

FLAMMABLE. AVOID FIRE, FLAME OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION.

Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperature above 120°F (49°C).

Keep out of reach of children.

Manufactured for : Connetics Corporation, Palo Alto, CA 94304, USA. October 2004. For additional information: 1-888-500-DERM or visit www.evoclin.com. FDA revision date: 7/11/2006

Last updated on RxList: 1/16/2009

The incidence of adverse events occurring in ≥ 1% of the patients in clinical studies comparing EVOCLIN and its vehicle is presented below:

Selected Adverse Events Occurring in ≥ 1% of Subjects

Adverse Event	Number (%) of Subjects
	Evoclin Foam N=439	Vehicle Foam N=154
Headache	12(3%)	1(%)
Application site burning	27(6%)	14(9%)
Application site pruritus	5(1%)	5(3%)
Application site dryness	4(1%)	5(3%)
Application site reaction, not otherwise specified	3(1%)	4(3%)

In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to EVOCLIN.

Orally and parenterally administered clindamycin has been associated with severe colitis, which may end fatally.

Cases of diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported as adverse reactions in patients treated with oral and parenteral formulations of clindamycin and rarely with topical clindamycin (see WARNINGS). Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin.

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.

Last updated on RxList: 1/16/2009

Orally and parenterally administered clindamycin has been associated with severe colitis, which may result in patient death. Use of the topical formulation of clindamycin results in absorption of the antibiotic from the skin surface. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin.

Studies indicate a toxin(s) produced by Clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Endoscopic examination may reveal pseudomembranous colitis. Stool culture for Clostridium difficileand stool assay for C. difficiletoxin may be helpful diagnostically.

When significant diarrhea occurs, the drug should be discontinued. Large bowel endoscopy should be considered to establish a definitive diagnosis in cases of severe diarrhea. Antiperistaltic agents, such as opiates and diphenoxylate with atropine, may prolong and/or worsen the condition.

Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of oral and parenteral therapy with clindamycin.

Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.

Avoid contact of EVOCLIN with eyes. If contact occurs, rinse eyes thoroughly with water.

General

EVOCLIN should be prescribed with caution in atopic individuals.

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenicity of a 1% clindamycin phosphate gel similar to EVOCLIN was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of EVOCLIN, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals.

A 1% clindamycin phosphate gel similar to EVOCLIN caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight.

Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.

Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.

Pregnancy: Teratogenic effects - Pregnancy Category B

Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher, and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from EVOCLIN based on a mg/m² comparison. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk following use of EVOCLIN. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of EVOCLIN in children under the age of 12 have not been studied.

Geriatric Use

The clinical study with EVOCLIN did not include sufficient numbers of patients aged 65 and over to determine if they respond differently than younger patients.

Last updated on RxList: 1/16/2009

Topically applied EVOCLIN may be absorbed in sufficient amounts to produce systemic effects (see WARNINGS).

EVOCLIN is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin, a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis.

Last updated on RxList: 1/16/2009

Pharmacokinetics

In an open label, parallel group study in 24 patients with acne vulgaris, 12 patients (3 male and 9 female) applied 4 grams of EVOCLIN Foam once-daily for five days, and 12 patients (7 male and 5 female) applied 4 grams of Clindagel® (clindamycin phosphate) Topical Gel, 1%, once daily for five days. On Day 5, the mean Cmax and AUC(0- 12) were 23% and 9% lower, respectively, for EVOCLIN Foam than for Clindagel®.

Following multiple applications of EVOCLIN Foam less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.

Microbiology

The clindamycin component has been shown to have in vitro activity against Propionibacterium acnes, an organism which is associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical trials with this product. Cross-resistance between clindamycin and erythromycin has been demonstrated.

Clinical Studies

In one multicenter, randomized, double-blind, vehicle-controlled clinical trial patients with mild to moderate acne vulgaris used EVOCLIN (clindamycin phosphate) Foam, 1% or the vehicle foam once daily for twelve weeks. Treatment response, defined as the proportion of patients clear or almost clear, based on the Investigator Static Global Assessment (ISGA), and the mean percent reductions in lesion counts at the end of treatment in this study are shown in the following table:

Efficacy Parameters	Evoclin Foam N= 386	Vehicle Foam N=127
Treatment response (ISGA)	31%	18%
Percent reduction in lesion counts
Inflammatory Lesions	49%	35%*
Noninflammatory Lesions	38%	27%*
Total Lesions	43%	31%*
*p < 0.05

Last updated on RxList: 1/16/2009

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 1/16/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CLINDAMYCIN - TOPICAL

(klin-duh-MY sin)

COMMON BRAND NAME(S): Cleocin T, Clinda-Derm

USES: This medication is used to treat acne. It helps to decrease the number of acne lesions. Clindamycin is an antibiotic which works by stopping the growth of bacteria.

HOW TO USE: Use this medication only on the skin. Clean and dry the affected area first.

If you are using the lotion, shake the bottle well before using. Apply a thin layer of medication usually twice a day or as directed by your doctor.

If you are using the medicated pad, wipe the affected area gently with it, then discard. Depending on the size of the area to be treated, more than one pad may be necessary.

If you are using the foam, apply it once daily to the affected areas. Use enough to cover the entire affected area. Do not spray the foam directly onto your hands or face, because the foam will begin to melt on contact with warm skin. Instead spray the amount needed directly into the cap or onto a cool surface such as a countertop. If the can seems warm or the foam seems runny, run the can under cold water. Please read the patient information leaflet available from your pharmacist for specific instructions on how to use the foam, and ask about any information that is unclear.

Wash your hands after use.

Avoid contact with your eyes, nose, mouth or any areas of broken skin. If you accidentally get medication in these areas, rinse well with plenty of cool water.

It may take between 2-6 weeks to notice an improvement in your condition, and up to 12 weeks to see the full benefit.

Inform your doctor if your condition does not improve or worsens.

SIDE EFFECTS: Burning, itching, dryness, redness, oily skin or skin peeling may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

A small amount of this medication may be absorbed into your bloodstream and may rarely cause a severe intestinal condition (pseudomembranous colitis) due to a resistant bacteria. This condition may occur while receiving treatment or even weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have the following symptoms because these products may make them worse. Tell your doctor immediately if you develop persistent diarrhea, abdominal or stomach pain/cramping, or blood/mucus in your stool.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using clindamycin, tell your doctor or pharmacist if you are allergic to it; or to lincomycin; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: chronic asthma or hay fever (atopic conditions), intestinal diseases (e.g., ulcerative colitis, enteritis).

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known if the medication in this product passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center 1-800-222-1222 (USA) or emergency room immediately. Canadian residents should call their local poison control center directly. This medication may be harmful if swallowed.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, apply it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store the US product at room temperature between 68-77 degrees F (20-25 degrees C)

Store the Canadian product at room temperature between 59-86 degrees F (15-30 degrees C).

Store the medication away from light and moisture. Keep containers tightly closed. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.